immunogenicity and safety of tnfa kinoid in rheumatoid arthritis with secondary resistance to tnfa antagonists

Conditions: Rheumatoid Arthritis

Summary: the objective of this trial is to demonstrate that active immunization with anti-tnfα kinoid (tnf-k) is able to induce polyclonal anti-tnfα antibodies in ra patients who were previously treated with anti-tnfα mab but have lost susceptibility to therapy.


Eligibility criteria:
inclusion criteria: * diagnosis of ra according to the revised 1987 criteria of the american college of rheumatology (acr) (arnett 1988) since at least six months prior to first study product administration. * male or female between 18 and 70 years of age at the time of the first immunization * active ra disease as evidenced by a disease activity score 28 (das 28) ≥ 3.2. * current or past treatment with an anti-tnf antagonist (infliximab, adalimumab,etanercept, certolizumab, golimumab). * a wash-out period before the first administration of the study product of at least ten weeks since the last administration of certolizumab or golimumab; at least eigth weeks since the last administration of infliximab; at least four weeks since the last administration of adalimumab or etanercept * history of positive response defined as an acr20 or das 28 decrease ≥ 1.2 or by the investigator opinion with previous tnfα antagonist treatment. * secondary treatment failure to maximum one previous tnfα antagonist treatment as defined by: * investigator opinion. or * das28 increase ≥ 0.6 during the last six months. or * decrease in european league against rheumatoid (eular) score. * written informed consent . exclusion criteria: * treatment with non-biological dmards within four weeks prior to first study product administration. mtx is allowed provided it is administered at as table dosage \< ou = 20 mg/week since at least 4 weeks. * treatment with any rheumatoid arthritis biological therapy other than tnfα antagonists at any time prior to first study product administration. * administration of high doses of intra-articular corticosteroids for the treatment of an acute mono-arthritis (eg knee) within 3 months prior to first study product administration. high dose of corticosteroids is defined as \> 50 mg triamcinolone or equivalent. * history of documented severe bacterial infection within 28 days prior to first immunization * history of primary resistance or intolerance to any tnfα antagonist. * history of or current congestive heart failure, controlled or not. * corticosteroids (prednisone or equivalent, \< ou = 10 mg per day) are allowed if they are administered at stable dosage since at lesat 4 weeks prior to the first immunization. inhaled and topical steroids are allowed. * known history of tuberculosis (tb). * suspicion of tb at chest x-rays at screening or within three months prior to first administration of study product. * suspicion of latent or active tuberculosis as defined by : * positive mantoux/purified protein derivative (ppd)test (\> ou = 5mm induration measured 48 to 72 hours after intradermal injection of tuberculin) at screening or within 30 days prior to first administration of study product. * and/or positive interferon-γ (ifn γ) tb diagnostic test (as measured by the elispot method) at screening or within three months prior to first administration of study product. * positive for hiv, hcv or hbv including hbsag and anti-hbc antibodies. * use of any investigational or non-registered product (drug or vaccine). * administration of any live vaccine within three months prior to study entry * any confirmed or suspected immunosuppressive or immunodeficient condition.

Keywords: rheumatoid arthritis anti-drug antibodies rheumatoid arthritis with secondary loss of efficacy to anti-tnfa antagonists and anti-drug antibodies